Persistent isolated C3 hypocomplementemia (PI-LowC3) is a reliable predictor of kidney failure in patients with proliferative lupus nephritis (LN), according to a recent study.

Based on a study of 197 patients with a median follow-up of 4.5 years, investigators found that PI-LowC3 at 6 months after a new diagnosis of proliferative LN was significantly associated with an approximately 2.5-fold increased risk for end-stage kidney disease (ESKD) or death and a 3.4-fold increased risk for ESKD after adjusting for age, sex, ethnicity, hypertension, and mycophenolate or cyclophosphamide use.

“Our findings support the use of PI-LowC3 as a low-cost readily available biomarker, allowing clinicians to modify treatment strategies early in the course of disease and offering a rationale for complement blockade trials in this particularly at-risk subgroup of LN patients,” Giovanni Maria Rossi, MD, of Parma University Hospital in Parma, Italy, and colleagues concluded in a paper published in Kidney International Reports.

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Proliferative LN progresses to ESKD in around 10% of the cases despite treatment, Dr Rossi’s team noted. Other than achieving proteinuria levels below 0.8 g/24h at 12 months after treatment, early biomarkers predicting ESKD or death are lacking, according to the investigators.

Of the 197 patients, 51 had PI-LowC3. The study population had a mean age of 36.3 years. All had at least 6 months of follow-up and serum C3 and C4 values available at the time of kidney biopsy and at 6 months of follow-up.

The authors concluded that PI-LowC3 “is arguably the first reliable early predictor of ESKD in LN identified in a large multiethnic cohort.”


Rossi GM, Maggiore U, Peyronel F, et al. Persistent isolated C3 hypocomplementemia as a strong predictor of end-stage kidney disease in lupus nephritis. Kidney Int Rep. Published online September 17, 2022. doi:10.1016/j.ekir.2022.09.012